LPS-induced nitric oxide

Some bisbibenzyls exhibited anti-inflammatory activity through the inhibition of LPS-induced nitric oxide synthase (NOS) in RAW 264.7 macrophages. Of the 19 bisbibenzyls tested, marchantin A (812) was the most potent (ICso 1.44 //M), which might involve in the inhibition of LPS-induced iNOS mRNA expression. The presence of phenolic hydroxyls and saturation at C-7, C-8 and/or C-7VC-8 are required for the inhibition of NO production [490]. 

Pujihara, M., Connolly, N., Ito, N., and Suzuki, T. (1994). Properties of protein kinase C isoforms (beta II, epsilon, and zeta) in a macrophage cell line (J774) and their roles in LPS-induced nitric oxide production. J Immunol 152, 1898-906. 

To set up and validate the in vitro systems we initiated a study with rat Uver slices. Stimulation by Upopolysaccharide (LPS) in liver slices was used to evoke a pro-inflammatory response in the Uver. Lipopolysaccharide (LPS), a component of Gram-negative bacterial ceU walls (also called endotoxin), has been associated with tissue injury and sepsis. In the Uver LPS activates the resident macrophages, the Kupffer ceUs, which results in cytokine release [96]. Furthermore, LPS is cleared by the Uver, mainly by Kupffer ceUs [97]. One of the major features of endotoxic shock is the induction of nitric oxide S5mthase in the Uver [98]. Inducible nitric oxide synthase (iNOS), the expression of which is induced by LPS and cytokines, produces nitric oxide (NO) in large quantities [99]. 

In addition to the inhibition of COX, lornoxicam shows weak inhibition of LPS-induced inducible nitric oxide synthase (iNOS IC50 65 pM) and LPS-induced interleukin-6 (IC50 54 pM), both of which could contribute to its potent anti-inflammatory and analgesic action (Berg et al., 1999). 

The innate pro-inflammatory response of these cells is activated upon exposure to LPS, prostaglandin or other TLR ligands, leading to production of classical proinflammatory cytokines including tumor necrosis factor (TNF)-a. On the other hand, classical activation by interferon (fFN)- /andLPS leads to production of TNF-a and also increased secretion of reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS). 

Skorokhod, O., Schwarzer, E., Ceretto, M., and Arese, P. (2007b). Malarial pigment hemo-zoin, IFN-gamma, TNF-alpha, IL-beta and LPS do not stimulate expression of inducible nitric oxide synthase production of nitric oxide in immunopurified human monocytes. Malaria J. 6, 73-81. 

Pu-erh tea, highly fermented, possesses a rich flavor and was long recognized as a tribute tea in the imperial court of China. Its major polyphenols are not well characterized, because of their insolubility in most extracting solvents, but are considered to be polymerized catechins of high molecular weight. The aqueous extract of pu-erh tea is active in inhibiting lipopolysaccharide (LPS)-induced inducible nitric oxide synthase activity. ... 

Chesrown, S. E., Monnier, J., Visner, G., and Nick, H. S. (1994). Regulation of inducible nitric oxide synthase mRNA levels by LPS, INF-y, TGF-j8, and IL-10 in murine macrophage... 

BH4 = Tetrahydrobiopterin CAM = Cytotoxic activated macrophage cNOS = Constitutive nitric oxide synthase CPR = Cytochrome P450 reductase EDRF = Endothelial-derived relaxation factor EPR = Electron paramagnetic resonance spectroscopy IL-1 = Interleukin-1 iNOS = Inducible nitric oxide synthase LPS = Lipopo-lysaccharide, or endotoxin NMMA = N -monomethyl-L-arginine NOS = Nitric oxide synthase ROS = Reactive oxygen species SOD = Superoxide dismutase TNF = Tumor necrosis factor. 

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